Padraig Harrington was born in Dublin, Ireland, the youngest of five sons of Patrick and Breda Harrington. His father, "Paddy" (1933–2005), a Garda who played Gaelic football for Cork in the 1950s, was also a boxer and hurler, and played to a five handicap in golf.

Harrington grew up in Rathfarnham, a middle-class area in Dublin's Southside and the birthplace of two other touring professional golfers -- Paul McGinley and Peter Lawrie. Harrington attended local secondary school Coláiste Éanna at the same time, but not in the same year/class, as McGinley, giving it the unique distinction of having produced two Ryder Cup golfers. Coached by Joseph McGinley, a golf enthusiast in the school, and Mark Hynes, local professional and first caddie, Harrington's interest and passion for the game grew, as the pair recorded their first victory together, in Stackstown G.C.

After a successful amateur career, including winning the Walker Cup with the Great Britain & Ireland team in 1995, Harrington turned professional later that year, joining the European Tour in 1996. Harrington came to professional golf at a relatively late age, having studied accountancy at university; he worked in that profession for a number of years while playing high-standard amateur golf. He was unsure whether to turn professional, initially doubting his skills.

His first victory came quickly, in the 1996 Peugeot Spanish Open. But for the next few years, the most remarkable thing about his career was the number of times he finished second in European Tour events without ever bettering that position, including four second-place finishes in five events in late 1999. However, in 2000 he discovered a winning touch, and he had at least one win on the European Tour each year from then up to 2004. He has finished in the top 10 on the European Tour's Order of Merit seven times, including second places in 2001 and 2002 and third places in 2003 and 2004 and eventually won the Order of Merit in 2006. Harrington won the European Tour Golfer of the Year award in 2007 and 2008.

From around 2000, Harrington appeared with increasing frequency in the U.S. at the majors and World Golf Championships events, and as a sponsor's invitee. He won his first professional event in the U.S. at the Target World Challenge, a non-PGA Tour event hosted by Tiger Woods, in 2002. In both 2003 and 2004 he was the runner up in the Players Championship, and in the latter year he won enough money on the PGA Tour as a non-member to earn an invitation to the end of season Tour Championship.

At the 2007 Open Championship, Harrington defeated Sergio García in a four-hole playoff at Carnoustie Golf Links, becoming the first Irishman to win The Open Championship in 60 years, and the first ever from the Republic of Ireland. Both players went into the playoff having shot a 7-under 277 for the championship. Harrington subsequently won by one stroke in the playoff.

A year later at the 2008 Open Championship, it was unclear if he would get a chance to defend his Open title at Royal Birkdale as eight days prior to the event he injured his wrist. But Harrington successfully defended his title, overcoming a two-shot deficit to Greg Norman with a final-round 69. He shot a 4-under-par 32 on the back nine, which enabled him to pull away from Norman and Ian Poulter. His eagle on the par-5 17th all but sealed the tournament. He was the first European golfer since James Braid in 1906 to retain the Claret Jug. The win moved him from 14th to third in the world rankings, behind only Tiger Woods and Phil Mickelson.

Just three weeks after winning the Open Championship, Harrington won the PGA Championship over the South Course of Oakland Hills Country Club outside Detroit, Mich., for his third major. Although at 5 over par after two rounds, he shot 8 under par for the weekend, carding successive scores of 66 in the third and fourth rounds. His 3-under-par 277 was two shots ahead of Sergio García and Ben Curtis. Harrington became the first European to win the PGA Championship in 78 years (Tommy Armour in 1930), and the first winner from Ireland.

Harrington's victory in the PGA Championship secured his position as the No. 1 player in Europe, earning him the top spot in the 2008 European Ryder Cup team under captain Nick Faldo.

Harrington has known his wife Caroline since childhood. They were married in 1997 and have two sons: Patrick, born in 2003, and Ciarán, born in November 2007.

Harrington became a Global Ambassador for Special Olympics, the world's largest sports organisation for people with intellectual disabilities, in May 2010. He has conducted a number of golf clinics for Special Olympics athletes and coaches. The red shoe laces Harrington wears on the golfing circuit to raise awareness for Special Olympics have captured the attention of golf commentators and fans around the world. He also has been a patron of Irish charity Oesophageal Cancer Fund (OCF) since 2006, having lost his father to oesophageal cancer in 2005, and actively promotes Lollipop Day, the designated day for oesophageal cancer fundraising in Ireland celebrated every February.